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@ARTICLE{Ugai:186779,
author = {T. Ugai and N. Akimoto and K. Haruki and T. A. Harrison and
Y. Cao and C. Qu and A. T. Chan and P. T. Campbell and S. I.
Berndt and D. D. Buchanan and A. J. Cross and B. Diergaarde
and S. J. Gallinger and M. J. Gunter and S. Harlid and A.
Hidaka and M. Hoffmeister$^*$ and H. Brenner$^*$ and J.
Chang-Claude$^*$ and L. Hsu and M. A. Jenkins and Y. Lin and
R. L. Milne and V. Moreno and P. A. Newcomb and R. Nishihara
and M. Obon-Santacana and R. K. Pai and L. C. Sakoda and R.
E. Schoen and M. L. Slattery and W. Sun and E. Amitay$^*$
and E. Alwers$^*$ and S. N. Thibodeau and A. E. Toland and
B. Van Guelpen and S. H. Zaidi and J. D. Potter and J. A.
Meyerhardt and M. Giannakis and M. Song and J. A. Nowak and
U. Peters and A. I. Phipps and S. Ogino},
title = {{P}rognostic role of detailed colorectal location and tumor
molecular features: analyses of 13,101 colorectal cancer
patients including 2994 early-onset cases.},
journal = {Journal of gastroenterology},
volume = {58},
number = {3},
issn = {0944-1174},
address = {Tokyo},
publisher = {Springer},
reportid = {DKFZ-2023-00107},
pages = {229-245},
year = {2023},
note = {2023 Mar;58(3):229-245},
abstract = {The pathogenic effect of colorectal tumor molecular
features may be influenced by several factors, including
those related to microbiota, inflammation, metabolism, and
epigenetics, which may change along colorectal segments. We
hypothesized that the prognostic association of colon cancer
location might differ by tumor molecular
characteristics.Utilizing a consortium dataset of 13,101
colorectal cancer cases, including 2994 early-onset cases,
we conducted survival analyses of detailed tumor location
stratified by statuses of microsatellite instability (MSI),
CpG island methylator phenotype (CIMP), and KRAS and BRAF
oncogenic mutation.There was a statistically significant
trend for better colon cancer-specific survival in relation
to tumor location from the cecum to sigmoid colon (Ptrend =
0.002), excluding the rectum. The prognostic association of
colon location differed by MSI status (Pinteraction =
0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid
trend for better colon cancer-specific survival [Ptrend <
0.001; multivariable hazard ratio (HR) for the sigmoid colon
(vs. cecum), 0.80; $95\%$ confidence interval (CI)
0.70-0.92], whereas MSI-high tumors demonstrated a
suggestive cecum-to-sigmoid trend for worse survival (Ptrend
= 0.020; the corresponding HR, 2.13; $95\%$ CI 1.15-3.92).
The prognostic association of colon tumor location also
differed by CIMP status (Pinteraction = 0.003) but not
significantly by age, stage, or other features. Furthermore,
MSI-high status was a favorable prognostic indicator in all
stages.Both detailed colonic location and tumor molecular
features need to be accounted for colon cancer
prognostication to advance precision medicine. Our study
indicates the important role of large-scale studies to
robustly examine detailed colonic subsites in molecular
oncology research.},
keywords = {Biogeography (Other) / Epigenetics (Other) / Mismatch
repair (Other) / Molecular pathological epidemiology (Other)
/ Young-onset cancer (Other)},
cin = {C070 / C120 / HD01 / C020},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36648535},
doi = {10.1007/s00535-023-01955-2},
url = {https://inrepo02.dkfz.de/record/186779},
}